Abstract
BACKGROUND AND AIM: MicroRNAs (miRNAs) play a key role in regulating gene expression within the tumor microenvironment, influencing cancer progression and therapy response. Cancer-associated fibroblasts (CAFs) contribute to tumor development by secreting exosomal miRNAs that promote proliferation, invasion, and resistance. This systematic review evaluates the impact of CAF-derived miRNAs on head and neck malignancies. METHODS: A systematic search was conducted in PubMed, Scopus, WOS, and Google Scholar following PRISMA guidelines. Studies focusing on CAF-derived miRNAs in head and neck cancers were included. Data extraction covered study characteristics, miRNA profiling methods, functional roles, and clinical significance. The Scirap tool was used for quality assessment. RESULTS: Among 921 identified articles, 21 met the inclusion criteria. Findings indicate that miR-21-5p, miR-106-5p, and miR-196a drive tumor progression in oral squamous cell carcinoma (OSCC), while miR-124 and miR-34a-5p act as suppressors. In esophageal squamous cell carcinoma (ESCC), miR-21 and miR-27a/b contribute to chemotherapy resistance, whereas miR-100-5p inhibits lymphangiogenesis. In head and neck squamous cell carcinoma (HNSCC), miR-196a and miR-196b may serve as diagnostic biomarkers. Exosomal miR-106a-5p promotes nasopharyngeal carcinoma (NPC) metastasis, and miR-7 and miR-196a contribute to therapy resistance in head and neck cancer (HNC). CONCLUSION: CAF-derived miRNAs significantly influence tumor progression, metastasis, and therapy resistance. These findings highlight their potential as biomarkers and therapeutic targets, warranting further clinical research for personalized treatment strategies.